Abstract
Background and Objectives: Non-alcoholic fatty liver disease is a worldwide significant public health problem, particularly in patients with type 2 diabetes mellitus. Identifying possible risk factors for the disease is mandatory for a better understandingand management of this condition. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been linked to the development and evolution of fatty liver but not to insulin resistance. The aim of this study isto evaluate the relationships between PNPLA3 and fatty liver, metabolic syndrome and subclinical atherosclerosis. Materials and Methods: The study group consisted of patients with type 2 diabetes mellitus without insulin treatment. The degree of liver fat loading was assessed by ultrasonography, and subclinical atherosclerosis was assessed using carotid intima-media thickness (CIMT). PNPLA3 rs738409 genotype determination was performed by high-resolution melting analysis that allowed three standard genotypes: CC, CG, and GG. Results: Among the 92 patients, more than 90% showed various degrees of hepatic steatosis, almost 62% presented values over the normal limit for the CIMT. The majority of the included subjects met the criteria for metabolic syndrome. Genotyping of PNPLA3 in 68 patients showed that the difference between subjects without steatosis and subjects with hepatic steatosis was due to the higher frequency of genotype GG. The CC genotype was the most common in the group we studied and was significantly more frequent in the group of subjects with severe steatosis; the GG genotype was significantly more frequent in subjects with moderate steatosis; the frequency of the CG genotype was not significantly different among the groups.When we divided the group of subjects into two groups: those with no or mild steatosis and those with moderate or severe steatosis it was shown that the frequency of the GG genotype was significantly higher in the group of subjects with moderate or severe steatosis. PNPLA3 genotypes were not associated with metabolic syndrome, subclinical atherosclerosis, or insulin resistance. Conclusions: Our results suggest that PNPLA3 does not independently influence cardiovascular risk in patients with type 2 diabetes mellitus. The hypothesis that PNPLA3 may have a cardioprotective effect requires future confirmation.
Highlights
Nonalcoholic fatty liver disease (NAFLD) comprises a large spectrum of disorders from simple fat loading of the liver to hepatic inflammation (NASH—nonalcoholic steatohepatitis), fibrosis, and cirrhosis, with its well-known complication, hepatocarcinoma [1]
We performed an observational study on subjects with type 2 diabetes mellitus who did not receive insulin treatment, investigated in the Clinical Center for Diabetes, Nutrition and Metabolic Diseases of “Sf. Spiridon” Emergency Hospital Ias, i over a period of 18 months.The patients were evaluated in an outpatient—ambulatory setting
The CC genotype was the most common in the group we studied, with no statistical differences between men and women (p = 0.297) (Table 4) and was significantly more frequent in the group of subjects with severe steatosis (73.68% compared to 48% in those with moderate steatosis; p = 0.04) (Table 5); the GG genotype was significantly more frequent in subjects with moderate steatosis (28% compared to 5.26% in those with severe steatosis; p = 0.03); the frequency of the CG genotype was not significantly different among the groups (p > 0.05)
Summary
Nonalcoholic fatty liver disease (NAFLD) comprises a large spectrum of disorders from simple fat loading of the liver (hepatic steatosis—defined by a hepatocytic fat loading of at least 5%) to hepatic inflammation (NASH—nonalcoholic steatohepatitis), fibrosis, and cirrhosis, with its well-known complication, hepatocarcinoma [1]. Only a small percentage of patients with hepatic steatosis will develop severe hepatic disorders, subjects with type 2 diabetes mellitus present an even higher risk of hepatocarcinoma [6]. Subjects with fatty liver have been shown to have a higher risk for surgical interventions and a higher rate of cancer in their first-degree relatives [7]. Non-alcoholic fatty liver disease is a worldwide significant public health problem, in patients with type 2 diabetes mellitus. The aim of this study isto evaluate the relationships between PNPLA3 and fatty liver, metabolic syndrome and subclinical atherosclerosis. PNPLA3 genotypes were not associated with metabolic syndrome, subclinical atherosclerosis, or insulin resistance. Conclusions: Our results suggest that PNPLA3 does not independently influence cardiovascular risk in patients with type 2 diabetes mellitus. The hypothesis that PNPLA3 may have a cardioprotective effect requires future confirmation
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